Array printing

Abstract

The invention provides a method of printing, onto a substrate ( 12 ), an array ( 14 ) of spots of reagent compositions for use in a chemical and/or biochemical analysis. The method includes displacing an array of reagent composition containing capillary tubes ( 22 ) arranged alongside one another from an inoperative position to an operative position in which open ends of the capillary tubes ( 22 ) simultaneously impinge against a substrate and thereafter displacing the array of tubes ( 22 ) from the operative position back to the inoperative position. The invention extends to a printing apparatus ( 10 ), a method of printing a layered array of spots of reagent compositions, a method of introducing reagent compositions into the tubes, a reagent introducing device for introducing reagent compositions into the tubes and a printing installation which includes the printing apparatus ( 10 ) and the reagent introducing device.

What is claimed is: 
     
       1. A method of printing, onto a substrate, layered arrays of spots, which method includes:
 forming an array of capillary tubes in or against a stackable supporting element, each capillary tube having at least one open end; 
 stacking a plurality of the stackable supporting elements side-by-side into a print head assembly, with each supporting element supporting an array of capillary tubes 
 using the array of capillary tubes to print a first array of spots onto the substrate; 
 allowing the first array of spots to dry; 
 printing, over the first array of spots, a second array of spots, the spots of the second array being at least partially coincident with the spots of the first array; 
 allowing the second array of spots to dry; 
 printing, over the second array of spots, a third array of spots, the spots of the third array being at least partially coincident with the spots of the second array; and 
 allowing the third array of spots to dry. 
 
     
     
       2. The method of  claim 1 , further comprising including a nucleic acid solution in one of the arrays of spots. 
     
     
       3. The method of  claim 1 , further comprising including a transfection reagent in one of the arrays of spots. 
     
     
       4. The method of  claim 1 , further comprising including a gelatin solution in one of the arrays of spots. 
     
     
       5. The method of  claim 1 , wherein the first array of spots includes a nucleic acid solution, the second array of spots includes a transfection agent, and the third array of spots includes a gelatin and sucrose solution. 
     
     
       6. The method of  claim 1 , further comprising overlaying cells over at least one of the arrays of spots. 
     
     
       7. The method of  claim 1 , further comprising overlaying mammalian cells over the third array of spots. 
     
     
       8. The method of  claim 6 , further comprising placing the cells and at least one array of spots into culture for at least 48 hours. 
     
     
       9. The method of  claim 6 , further comprising chemically fixing and staining the cells with antibodies, and imaging the cells. 
     
     
       10. The method of  claim 6 , wherein 150 to 210 cells are overlaid per spot. 
     
     
       11. The method of  claim 1 , further comprising allowing the first array of spots to dry for 48-72 hours. 
     
     
       12. The method of  claim 1 , further comprising allowing the second array of spots to dry for 72-96 hours. 
     
     
       13. The method of  claim 1 , further comprising allowing the third array of spots to dry for 3-5 days. 
     
     
       14. The method of  claim 1 , further comprising including a fluorescent dye in one of the arrays of spots, and imaging the spots using a fluorescent imaging device. 
     
     
       15. The method of  claim 2 , wherein the nucleic acid solution includes an RNA and an expression vector. 
     
     
       16. The method of  claim 15 , wherein the RNA in the nucleic acid solution includes an siRNA, a μRNA, or a non-coding RNA. 
     
     
       17. The method of  claim 15 , wherein the expression vector in the nucleic acid solution includes a cDNA expression, or an shRNA expression. 
     
     
       18. The method of  claim 2 , wherein the nucleic acid solution includes a fluorescent dye labelled nucleotide and an siRNA directed toward NFkB subunit p65. 
     
     
       19. The method of  claim 1 , further comprising storing one of the printed arrays before overlay printing of another array. 
     
     
       20. The method of  claim 1 , further comprising printing one of the arrays of spots using 330 μm outer diameter capillary tubes. 
     
     
       21. The method of  claim 1 , further comprising printing one of the arrays of spots using 400 μm outer diameter capillary tubes. 
     
     
       22. The method of  claim 1 , wherein at least one printed array of spots includes spots of a different size to spots included in another array of printed spots. 
     
     
       23. The method of  claim 4 , wherein the concentration of gelatin in the gelatin solution is in the range 0.4% to 3.2% w/v. 
     
     
       24. The method of  claim 1 , wherein the first, second and third arrays of spots substantially coincide and form layered transfection arrays on the substrate when dry. 
     
     
       25. The method of  claim 1 , wherein the layered arrays of spots of reagent compositions are each printed by:
 displacing an array of reagent composition containing capillary tubes arranged alongside one another and each having at least one open end, with the open ends of the tubes being aligned, from an inoperative position to an operative position in which the open ends of the capillary tubes simultaneously impinge against a substrate, so that at least some reagent composition from the capillary tubes is thereby deposited on the substrate as spots, thereby to form an array of spots of the reagent compositions on the substrate; and 
 thereafter displacing the array of capillary tubes from the operative position back to the inoperative position. 
 
     
     
       26. The method of  claim 25 , further including, after the array of capillary tubes has been displaced back to its inoperative position, or while it is being so displaced, replacing the substrate bearing the array of spots with another substrate, and repeating the displacement of the array of capillary tubes from its inoperative position to its operative position, and back to its inoperative position. 
     
     
       27. The method of  claim 26 , further including, before the displacing of the array of capillary tubes from the inoperative position to the operative position, forming the array of capillary tubes by supporting the capillary tubes on or against a plurality of supporting elements, with each supporting element supporting a plurality of the tubes and stacking the supporting elements into a print head assembly, with the displacing of the capillary tubes being effected by moving the print head assembly.